Objective: Globally, waterpipe (WP) smoking is becoming a more prevalent form of tobacco consumption. Whilst research so far has demonstrated a significant link between WP use and a number of health outcomes, little is known of its association with heart disease. We examine in this study the association of WP smoking with angiographically confirmed coronary artery disease (CAD). Methods: A total of 1210 patients, aged 40 years and over and free from smoking-associated illnesses or history of cardiovascular procedures, admitted for coronary angiography at four major hospitals in Lebanon, were included. The extent of CAD was summarized in two ways, firstly as diseased (≥50% and ≥70% occlusion in at least one main coronary artery) versus non-diseased (entirely normal coronaries), and secondly, as CAD cumulative score based on Duke CAD Prognostic Index. A score of WP-years, capturing intensity and lifetime duration of exposure, was estimated for each individual. Results: Lifetime exposure exceeding 40 WP-years was associated with a threefold significant increase in the odds of having severe stenosis (≥70%) compared to non-smokers (OR=2.94, 95% CI 1.04-8.33) as well as with the CAD Index (β=7.835, p-value=0.027), net of the effect of socio-demographic characteristics, health behaviors and co-morbidity. A dose-response relationship between WP-years and percent stenosis was also established. WP smoking status (never, past and current) did not associate with CAD. Conclusions: Cumulative exposure to WP smoking is significantly associated with severe CAD. There is a need to monitor WP use among cardiac patients and include this information in their medical charts in the same manner cigarettes smoking is documented. This is likely to increase awareness of the hazards of WP smoking and prompt physicians to target WP tobacco control by providing advice to their patients on WP smoking cessation.